The scope of this special initiative is to develop a research program concerned with how elderly people differ from younger people in their response to drugs. Three projects are being carried out. One is to learn about how the pharmacokinetics of basic drugs excreted by the kidney are altered in the elderly over and above any slowing of excretion due to decline in overall renal function as measured by the glomerular filtration rate. We are also studying the extent to which drug and chemical nephrotoxicity contributes to the decline in GFR that occurs with aging. The second project is to learn how aging modifies the pharmacokinetics of narcotic analgesics and the intensity of their pharmacologic effects. The third project is to learn how aging modifies the effects of drug-induced stimulus-bound repetitive discharge of fast and slow gamma-motor nerve terminals.